2007 melvin tooker animal improvement programs laboratory usda agricultural research service,...
TRANSCRIPT
2007
Melvin Tooker Melvin Tooker Animal Improvement Programs Laboratory USDA Agricultural Research Service, Beltsville, MD, USA [email protected]
2009
An Introduction to An Introduction to GenomicsGenomics
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Genomic GoalsGenomic Goals
Predict young bulls and cows more accurately
Compare actual DNA inherited Use exact relationship matrix G
instead of expected values in A Trace chromosome segments Locate genes with large effects
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Short historyShort history Illumina BovineSNP50™ BeadChip developed
Accuracy of genomic information assessed by using 2004 evaluations of bulls born before 2000 to predict 2009 evaluations of young bulls
Unofficial genomic evaluations of bull calves provided to industry beginning in April 2008
Jersey results released in October 2008
Over 23,000 animals genotyped through Mar. 2009
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Source of genomic evaluationsSource of genomic evaluations DNA extracted from blood, hair, or semen
~40,000 genetic markers (SNPs) evaluated
For each SNP, difference in PTA estimated between animals with 1 allele compared to the other allele
Genomic data contribute ~11 daughter equivalents to reliability
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How Related are Relatives?How Related are Relatives?
Example: Full sibs • are expected to share 50% of their
DNA on average • may actually share 45% or 55% of
their DNA because each inherits a different mixture of chromosome segments from the two parents.
Combine genotype and pedigree data to determine exact fractions
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Genomic RelationshipsGenomic Relationships
Measures of genetic similarity• A = Expected % genes identical by
descent from pedigree (Wright, 1922)• G = Actual % of DNA shared (using
genotype data)• T = % genes shared that affect a
given trait (using genotype and phenotype)
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Markers vs QTLsMarkers vs QTLs
Models contain markers, not QTLs• M is markers inherited minus freq• M M’ / ∑ p(1-p) = G
List all QTL affecting a trait• Q is alleles inherited minus freq• q contains effects of alleles• u = Q q , var(q) = Vq
• var(u) = E(u u’) = Q Vq Q’ = T
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QTL Relationship Matrix (QTL Relationship Matrix (TT) )
Three bulls have +50 PTA protein. Do they have the same genes?
• Extremely unlikely.• Bull A could have 10 positive genes.• Bull B could have 10 positive genes,
but on different chromosomes.• Bull C could have 20 positive and 10
negative genes.
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Genes in Common at One LocusGenes in Common at One Locus
If Full Sib 1 inherits:
If Full Sib 2 inherits:
w,y w,z x,y x,z
w,y 2 1 1 0
w,z 1 2 0 1
x,y 1 0 2 1
x,z 0 1 1 2
w = gene from sire of sirex = gene from dam of sirey = gene from sire of damz = gene from dam of dam
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Unrelated Individuals?Unrelated Individuals?
No known common ancestors Many unknown common ancestors
born before the known pedigree Relationships in base
• 0 ± x.x% due to earlier ancestors• Called linkage disequilibrium (LD)• Poor terminology, genes may not be
physically linked
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Traditional PedigreeTraditional Pedigree
Sire of Sire
Sire
Dam of Sire
Animal
Sire of Dam
Dam
Dam of Dam
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Genomic PedigreeGenomic Pedigree
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Example of a SNP haplotypeExample of a SNP haplotype
caacgtat
caacggat
SNP
atccgaat
atccgcat
…
… …
…
SNP
tctaggat
tctcggat
SNP
…
…Chr1
Chr2
Haplotype is a set of single nucleotide polymorphisms (SNPs) associated on a single chromosome. Identification of a few alleles of a haplotype block can identify other polymorphic sites in the region.
Haplotype 1 tca
gac Haplotype 2
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SNP PedigreeSNP Pedigreeatagatcgatcg
ctgtagcttagg
agggcgcgcagt
cgatctagatcg
cggtagatcagt
agagatcgatct
atggcgcgaacg
ctatcgctcagg
ctgtagcgatcg
agatctagatcg
agagatcgcagt
atgtcgctcacg
ctgtctagatcg
atgtcgcgcagt
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Haplotype PedigreeHaplotype Pedigreeatagatcgatcg
ctgtagcttagg
agggcgcgcagt
cgatctagatcg
cggtagatcagt
agagatcgatct
atggcgcgaacg
ctatcgctcagg
ctgtagcgatcg
agatctagatcg
agagatcgcagt
atgtcgctcacg
ctgtctagatcg
atgtcgcgcagt
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Translate Haplotype to GenotypeTranslate Haplotype to Genotype
agatctagatcg
111211120200
ctgtagcgatcg
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Genotype PedigreeGenotype PedigreeCount number of second alleleCount number of second allele
121101011110
111211120200
101121101111
122221121111
101101111102
011111012011
121120011010
0 = homozygous for first allele (alphabetically)1 = heterozygous2 = homozygous for second allele (alphabetically)
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Genotype Data for ElevationGenotype Data for Elevation Chromosome 1Chromosome 1
10001112200200121110111121111011110011211000201220022201111202101200211122110021112001111001011011010220011002201101120020110102022212112210201001110001122022122211202112012020100202202000021100011202011221112111022011110000212202000221012020002211220111012100111211102112110020102100022000220100020110000220221102211210112111012222001211212220020002002020201222110022222220022121111210021111200110111011200202220001112011010211121211102022100211201211001111102111211021112200010110111020220022111010201112111101120210210212110110221220012110112110120220110022200210021100011100211021101110002220020221212110002220102002222121221121112002011020200122222211221202121121011001211011020022000200100200011110110012110212121112010101212022101010111110211021122111111212111210110120011111021111011111220121012121101022202021211222120222002121210121210201100111222121101
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Genotype Data from Inbred BullGenotype Data from Inbred BullChromosome 24 of MegastarChromosome 24 of Megastar
102122210102102101110211011211221121100220200022202000202022000002200202222022020000200202222220000202222000002202000020022002000000222200022220000000000020222022002000222020222220002202222222220000200220202220200020002200000000220222000000220020200022220020200200202022202222222202220200020220220222202022202020202200022002220220022200000220200002002002000200222220002222020200222002220200002020000002222202020000200200222200020220222200220002222022002222020200022022022220022200220002002202000002200220222000022000022000222202002222000220020020202202000222000222002220220220000022022002002002022000200022220220022200202202002222022200000202200020200202020002200220000022022200202220200022002000200022002002000200220222220022022000200002000200002022002022020020000222000022200200020022200002202200200220022022020202020202000222020002202002022022202200002020200002020200022222200222200020022022220000020220020200202022022020200002000200220220002200
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Genotype Parents and Grandparents
Manfred
O-Man
Jezebel
O-Style
Teamster
Deva
Dima
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Expected Relationship MatrixExpected Relationship Matrix11
1HO9167 O-Style1HO9167 O-Style
PGS PGD MGS MGD Sire Dam Bull
Manfred 1.0 .0 .0 .0 .5 .0 .25
Jezebel .0 1.0 .0 .0 .5 .0 .25
Teamster .0 .0 1.0 . 0 .0 .5 .25
Dima .0 .0 .0 1.0 .0 .5 .25
O-Man .5 .5 .0 .0 1.0 .0 .5
Deva .0 .0 .5 .5 .0 1.0 .5
O-Style .25 .25 .25 .25 .5 .5 1.0
1Calculated assuming that all grandparents are unrelated
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Pedigree Relationship MatrixPedigree Relationship Matrix1HO9167 O-Style1HO9167 O-Style
PGS PGD MGS MGD Sire Dam Bull
Manfred 1.053 .090 .090 .105 .571 .098 .334
Jezebel .090 1.037 .051 .099 .563 .075 .319
Teamster .090 .051 1.035 .120 .071 .578 .324
Dima .105 .099 .120 1.042 .102 .581 .342
O-Man .571 .563 .071 .102 1.045 .086 .566
Deva .098 .075 .578 .581 .086 1.060 .573
O-Style .334 .319 .324 .342 .566 .573 1.043
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Genomic Relationship Matrix Genomic Relationship Matrix 1HO9167 O-Style1HO9167 O-Style
PGS PGD MGS MGD Sire Dam Bull
Manfred 1.201 .058 .050 .093 .609 .054 .344
Jezebel .058 1.131 .008 .135 .618 .079 .357
Teamster .050 .008 1.110 .100 .014 .613 .292
Dima .093 .135 .100 1.139 .131 .610 .401
O-Man .609 .618 .014 .131 1.166 .080 .626
Deva .054 .079 .613 .610 .080 1.148 .613
O-Style .344 .357 .292 .401 .626 .613 1.157
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Difference (Genomic – Pedigree) Difference (Genomic – Pedigree) 1HO9167 O-Style1HO9167 O-Style
PGS PGD MGS MGD Sire Dam Bull
Manfred .149 -.032 -.040 -.012 .038 -.043 .010
Jezebel -.032 .095 -.043 .036 .055 .004 .038
Teamster -.040 -.043 .075 -.021 -.057 .035 -.032
Dima -.012 .036 -.021 .097 .029 .029 .059
O-Man .038 .055 -.057 .029 .121 -.006 .060
Deva -.043 .004 .035 .029 -.006 .087 .040
O-Style .010 .038 -.032 .059 .060 .040 .114
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ConclusionsConclusions
Relationships can be defined as:• A = expected genes in common• G = actual DNA in common• T = QTL alleles in common for a trait
Full sibs share 50% ± 3.5% of DNA. “Unrelated” animals share more or
fewer unknown ancestors than average. Reliability can increase if genomic (G)
replace traditional (A) relationships
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Where are the Major Genes?Where are the Major Genes?
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Distribution of Marker Effects (Distribution of Marker Effects (Net MeritNet Merit))
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Distribution of Marker Effects (Distribution of Marker Effects (DPRDPR))
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Marker Effects on WebsiteMarker Effects on Website
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Marker Effects on WebsiteMarker Effects on Website
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Marker Effects on WebsiteMarker Effects on Website
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Positive or Negative TraitsPositive or Negative Traits
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From whom did the bad allele come?From whom did the bad allele come? Round Oak Rag Apple Elevation (7HO00058)
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Net Merit by ChromosomeNet Merit by ChromosomeFreddie (1HO08784)Freddie (1HO08784) - highest Net Merit bull - highest Net Merit bull
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Net Merit by ChromosomeNet Merit by Chromosome O Man (7HO06417)O Man (7HO06417) – Sire of Freddie – Sire of Freddie
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Net Merit by ChromosomeNet Merit by ChromosomeDie-Hard (29HO08538) Die-Hard (29HO08538) - maternal grandsire- maternal grandsire
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New Chromosomal PTA QueryNew Chromosomal PTA Query
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Chromosomal PTA Query ExampleChromosomal PTA Query Example
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AcknowledgmentsAcknowledgments
Genotyping and DNA extraction:• USDA Bovine Functional Genomics Lab, U.
Missouri, U. Alberta, GeneSeek, Genetics & IVF Institute, Genetic Visions, and Illumina
Computing: • AIPL staff (Mel Tooker, Leigh Walton, Jay
Megonigal) Funding:
• National Research Initiative grants– 2006-35205-16888, 2006-35205-167012006-35205-16888, 2006-35205-16701
• Agriculture Research Service• Holstein, Jersey & Brown Swiss breed associations• Contributors to Cooperative Dairy DNA Repository
(CDDR)